Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review

van Tilburg C M, Sanders E A, Rovers M M, Wolfs T F, Bierings M B

CRD summary

The authors concluded that chemotherapy in children with acute lymphocytic leukaemia is associated with a temporary reduction in antibody levels against specific diseases and re-vaccination may be required. The evidence was based on a very small number of children in few studies and the results varied widely across studies. This suggests that a more cautious conclusion might be appropriate.

Authors' objectives

To review the vaccination and re-vaccination status of children who have been treated for acute lymphocytic leukaemia (ALL).

Searching

PubMed and EMBASE were searched from January 1980 to January 2006 for peer-reviewed studies published in the English language after 1980. The search strategy was reported. In addition, reference lists in identified reports were screened, a 'related articles' search was undertaken, and ISI Web of Knowledge was scanned.

Study selection

Study designs of evaluations included in the review

Studies with at least 10 children per vaccine group were eligible for inclusion. Studies in which subgroups of less than 10 children had been re-vaccinated were excluded from the analysis. No other inclusion criteria were specified for study design.

Participants included in the review

Studies of children aged younger than 18 years who had been treated for ALL were eligible for inclusion. Studies of children who were still receiving chemotherapy were excluded. The included studies were conducted between 1973 and 2002.

Outcomes assessed in the review

Studies that reported the vaccination status of children in such a way that the percentage of protected children could be calculated were eligible for inclusion. The review assessed the percentage of children with protection before chemotherapy and after re-vaccination. The included studies varied in the timing of assessment of vaccination status post-chemotherapy (where reported, range: 0 to 168 months) and in the definition of the antibody level that was considered protective (details of levels used in the individual studies were reported, where possible, for each vaccine type).

How were decisions on the relevance of primary studies made?

Two reviewers independently selected the studies. Any disagreements were resolved by discussion.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Where possible, for each study, the percentages of children protected before and after chemotherapy and after re-vaccination were extracted and protection rates post-chemotherapy with 95% confidence intervals (CIs) were plotted graphically for each vaccine type.

Methods of synthesis

How were the studies combined?

The studies were grouped by vaccine type and the range of protection across studies was reported.

How were differences between studies investigated?

Differences between the studies were discussed.

Results of the review

Eight studies (n=340) were included. Some studies reported data from different numbers of children for different vaccine types.

Few studies reported pre-chemotherapy protection rates.

Diphtheria (5 studies, n=188): 3 studies reported post-chemotherapy protection rates above 80%. The other 2 studies reported post-chemotherapy protection rates of 17% and 33%; these studies reported re-vaccination protection rates of 87% and 100%, respectively. One of these studies (with a post-chemotherapy protection rate of 17%) reported a pre-chemotherapy protection rate of 39%. Post re-vaccination rates were not reported for any other studies.

HIB (3 studies, n=134): 1 study reported a pre-chemotherapy protection rate of 100% and a post-chemotherapy protection rate of 100% (using a titre of 0.15 microg/mL). Two studies reported post-chemotherapy protection rates of 35% and 75%. Post-vaccination protection rates rose from 75 to 83% in 1 study and were reported as 93% in another study that reported no other rates.

Mumps (3 studies, n=132), measles (4 studies, n=176) and rubella (3 studies, n=155): the studies used different definitions of protective antibody levels. One study reported a pre-chemotherapy protection rate for measles of 15 out of 16 patients and a post-chemotherapy protection rate of 60%. The studies reported a wide variation in post-chemotherapy protection rates (range: 29 to 92%. One study reported a pre-chemotherapy protection rate for rubella of 16 out of 16 patients and a post-chemotherapy protection rate of 72%. One study reported a post-chemotherapy protection rate of 29% for mumps, which rose to 66% after re-vaccination. The same study reported a post-chemotherapy protection rate of 29% for measles, which rose to 76% after re-vaccination. Other studies did not report protection rates after re-vaccination.

Authors' conclusions

Chemotherapy in children with ALL is associated with a temporary reduction in antibody levels against specific diseases and re-vaccination may be required.

CRD commentary

The review addressed a clear question that was defined in terms of the participants, intervention, outcomes and some aspects of study design. Several relevant sources were searched but no attempts were made to minimise either publication or language bias. Methods were used to minimise reviewer error and bias in the study selection process, but it was not clear whether similar steps were taken when extracting the data. Study validity was not assessed and little information was provided about the participants.

The results were presented as ranges of values of protection rates, which seemed appropriate given the diversity of the studies. Evidence regarding the drop in level of protection after chemotherapy and protection after re-vaccination was based on a very small number of children in few studies, and the protection rates varied considerably across studies. This suggests that a more cautious conclusion might have been more appropriate. In addition, incomplete reporting of review methods meant it was not possible to assess the reliability of the review.

Implications of the review for practice and research

Practice: The authors stated that decisions regarding the screening and re-vaccination of patients after chemotherapy should take account of the local situation (level of vaccination coverage and level of disease).

Research: The authors stated the need for larger, multicentre, prospective longitudinal studies to evaluate the effect of current ALL treatment regimens on immunity and its restoration in homogeneous populations of patients.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.